Clinical Investigations: Congestive Heart Failure
Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure*,**

https://doi.org/10.1067/mhj.2002.121463Get rights and content

Abstract

Objective The purpose of this study was to investigate whether long-term therapy with crataegus extract WS 1442 is efficacious as add-on therapy to preexisting diuretic treatment in patients with heart failure with a more advanced stage of the disease (New York Heart Association [NYHA] class III), whether effects are dose dependent, and whether the treatment is safe and well tolerated. Methods Exercise capacity was assessed by use of seated bicycle ergometry with incremental workloads. Scores for subjective symptoms and complaints made by the patients were analyzed. Efficacy and tolerability of the treatments were judged by both the patients and investigators. Safety was assessed by the documentation of adverse events and the safety laboratory. Results A total of 209 patients were randomized to treatment with 1800 mg of WS 1442, 900 mg of WS 1442, or with placebo. After 16 weeks of therapy with 1800 mg of WS 1442 per day, maximal tolerated workload during bicycle exercise showed a statistically significant increase in comparison with both placebo and 900 mg of WS 1442. Typical heart failure symptoms as rated by the patients were reduced to a greater extent by WS 1442 than by placebo. This difference was significant for both doses of WS 1442. Both efficacy and tolerability were rated best for the 1800 mg of WS 1442 group by patients and investigators alike. The incidence of adverse events was lowest in the 1800 mg of WS 1442 group, particularly with respect to dizziness and vertigo. Conclusions The data from this study confirm that there is a dose-dependent effect of WS 1442 on the exercise capacity of patients with heart failure and on typical heart failure-related clinical signs and symptoms. The drug was shown to be well tolerated and safe. (Am Heart J 2002;143:910-5.)

Section snippets

Patients

Male and female (postmenopausal or using reliable contraceptive methods) patients ≥40 years old with chronic congestive heart failure (NYHA class III) known for at least 6 months were eligible for participation in this study if they were previously untreated or treated with a diuretic and/or with a low dose of an angiotensin-converting enzyme (ACE) inhibitor and had an exercise capacity of ≤75 watts (W) as assessed by seated bicycle ergometry. Major exclusion criteria are listed in Table I.

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Results

In total, 232 patients were enrolled in the study. Of these, 23 patients discontinued the study before randomization and 209 patients (1800 mg of WS 1442 [n = 69], 900 mg of WS 1442 [n = 70], placebo [n = 70]) were randomized to treatment by 18 centers in Germany. All of them were included in the intention-to-treat analysis of efficacy and the safety evaluation. Twelve patients (1800 mg of WS 1442 [n = 1], 900 mg of WS 1442 [n = 7], placebo [n = 4]) were prematurely withdrawn from the study

Discussion

Previous randomized placebo-controlled studies that used exercise testing in patients with NYHA class II heart failure consistently demonstrated reductions in the effort-induced increases in heart rate, blood pressure, and the rate-pressure product.9, 10, 11, 15, 16, 17, 18, 20, 21v. Generally, exercise capacity improved, and in a study comparing crataegus extract (900 mg) with captopril, no difference between the treatments was observed. The improvements were statistically significant in both

Acknowledgements

The Clinical Research and Biometrics Units of Dr Willmar Schwabe GmbH & Co performed the data collection and the statistical analysis for this study. We thank all participating investigators for their contribution to the study: Dr Beudt-Jalladeau, Oberursel; Dr Hehmann, Idstein; Dr Wölfel, Alsbach-Hähnlein; Dr Hinkelmann, Kuppenheim; Dr Neugart, Villingen-Schwenningen; Dr Buntrock, Berlin; Dr Heinke, Tiefenbach; Dr Englert, Gars am Inn; Dr Adler, Ludwigshafen; Dr Schibalski, Johannisberg; Dr

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    *

    Supported by a grant from Dr Willmar Schwabe GmbH & Co, Karlsruhe, Germany.

    **

    Reprint requests: Prof Dr med M. Tauchert, Klinikum Leverkusen gGmbH, Dhunnberg 60, 51375 Leverkusen, Germany.

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